ArticlesComparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia
Introduction
Heart failure due to iron overload can develop either as a result of excess dietary absorption (hereditary haemochromatosis) or from repeated blood transfusions. The most striking model of cardiac iron overload is seen in thalassaemia major, in which heart failure remains the major cause of death (60%), greatly exceeding deaths from infection (13%) and liver disease (6%).1 Despite the introduction of the iron-chelating agent desferrioxamine more than 30 years ago in the UK, 50% of patients still die before reaching the age of 35 years.2 This high mortality is partly the result of difficulties with administration of desferrioxamine. This drug requires long subcutaneous or intravenous infusions on at least 4 days a week; compliance with treatment is inadequate in many cases. The need for an effective alternative approach with an oral iron chelator has long been acknowledged,3 and medium-term results from prospective trials of the oral chelator deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) seemed promising;4, 5, 6 however, the long-term effectiveness of this drug has been questioned because liver iron content is high in some patients.7, 8 Since the primary objective of iron-chelation therapy is to prevent the lethal cardiac complications from myocardial iron deposition, myocardial iron and ventricular function should also be taken into account in assessment of the effectiveness of chelating agents. New magnetic resonance techniques can assess both myocardial iron and ventricular function in the same study.9 Our aim, therefore, was to investigate whether deferiprone is effective in controlling myocardial iron.
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Participants
We included all patients based at the Whittington Hospital, London, UK, who received chelation with deferiprone alone for longer than 3 years (mean duration 5·7 years [SD 1·8]), between May, 1999, and December, 2000. For each deferiprone patient, we assigned two controls with thalassaemia major, matched for age, sex, and current ferritin concentration, who were receiving standard subcutaneous desferrioxamine. Controls were chosen from the thalassaemic population also treated at this centre. The
Results
Clinically relevant characteristics for patients in the two study groups are compared in table 1.
The deferiprone-treated group had significantly less myocardial iron than the desferrioxamine-treated group (median myocardial T2* 34·0 vs 11·4 ms, p=0·02, table 2). The deferiprone group also had a higher mean left-ventricular ejection fraction (p=0·004) and less left-ventricular dilatation in systole (p=0·03) and diastole (p=0·01) than the control group. The left-ventricular mass index was lower,
Discussion
The iron chelator desferrioxamine was introduced more than 30 years ago13, 14 and remains the only chelator approved for regular use in North America and the only first-line agent approved for use in Europe. Desferrioxamine improves hepatic, cardiac, and endocrine dysfunction and lengthens survival in patients with iron overload.15, 16, 17 The disadvantages include high cost,18 the requirement for daily parenteral administration, and local and systemic toxic effects, which include visual19 and
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